Acetic Anhydride → Butanoic acid, 2-(ethoxymethylene)-4,4-difluoro-3-oxo-, ethyl ester

HRID 2280350Notes

Reaction equation

HRID 2280350 reaction equation
[F:1][CH:2]([F:11])[C:3](=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH:12](OCC)(OCC)[O:13][CH2:14][CH3:15].C(OC(=O)C)(=O)C>>[CH2:14]([O:13][CH:12]=[C:4]([C:3]([CH:2]([F:11])[F:1])=[O:10])[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:15]

Participants

4

Reactant 3

HCID 7918Acetic AnhydrideHCID 31214Ethyl orthoformateHCID 67697Ethyl 4,4-difluoroacetoacetate2×

Product 1

HCID 53395411Butanoic acid, 2-(ethoxymethylene)-4,4-difluoro-3-oxo-, ethyl esterYield 86.4%

Conditions

Temperature
92.5 °C

Procedure

To the concentrated product of crude ethyl difluoroacetoacetate (˜0.93 mole) are added triethyl orthoformate (266.8 g, 1.8 moles) and acetic anhydride (367.6 g, 3.6 moles). The mixture is heated to 90-95° C., and kept gently refluxing for 6 hours. (GC shows ethyl difluoroacetoacetate content <0.1%). The reaction mixture is cooled to 60-70° C. and then concentrated under vacuum to remove excess acetic anhydride, triethyl orthoformate, and generated ethyl acetate. A pale brown liquid (178.6 g) is obtained. The yield of two steps is 80%.

Workup

  1. temperaturekept gently refluxing for 6 hours
  2. temperatureThe reaction mixture is cooled to 60-70° C.
  3. concentrationconcentrated under vacuum
  4. customto remove excess acetic anhydride, triethyl orthoformate

Sources & evidence

ORD record
ord-081d3386183040a48406e367238dcd9f
Source dataset
uspto-grants-2015_09
Patent number
US09139507B2

Reaction notes

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